Browsing by Author "Reinert, Shannon"
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Item Role of KIRREL in Mammalian Myogenesis and Rhabdomyosarcoma(2018-01-23) Reinert, Shannon; Avirneni, Usha; Galindo, ReneRhabdomyosarcoma is an aggressive soft-tissue malignancy comprised microscopically of neoplastic skeletal muscle-lineage precursors that fail to exit the cell-cycle and fuse into syncytial muscle - the underlying pathogenetic mechanisms for which remain unclear. We previously identified that misregulated myoblast fusion signaling via the TANC1 adaptor molecule promotes neoplastic transformation in RMS cells driven by the PAX-FOXO1 oncogenic transcription factor. Unknown from these studies are the upstream elements that participate with TANC1 in wild-type myoblasts to orchestrate myoblast fusion, and how these elements likewise participate in RMS. We are now interrogating the Immunoglobulin Superfamily Receptor Kirrel receptors in these processes. Three Kirrel orthologs are present in mammals, two of which, Kirrel-1 and -3, are expressed normally in myogenesis. Using loss-of-function (shRNA) and gain-of-function (misexpression) strategies, our preliminary data are showing a requirement for Kirrel-3 during myoblast fusion, as tube formation is significantly altered in these studies. We are now extending these for Kirrel-3 activity in RMS using cultured neoplastic rhabdomyoblast. Our data and most recent findings will be presented and discussed.